Abiraterone ((3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-ol) is a drug used in the treatment of patients with castration-resistant prostate cancer (CRPC). It is formulated as its prodrug—Abiraterone acetate ((3β)17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate) and sold under the brand name Zytiga. Zytiga in combination with prednisone is indicated for the treatment of patients with metastatic CRPC who have received prior chemotherapy containing docetaxel.
U.S. Pat. No. 5,604,213 discloses a method for preparation of Abiraterone acetate by palladium-catalyzed cross-coupling of steroidal 17-enol triflate (2) with a suitable pyridyl-containing nucleophilic coupling partner (Scheme 1):

According to U.S. Pat. No. 5,604,213, dehydroepiandrosterone 3-acetate was converted into its 17-enol triflate (2) by a base-catalyzed reaction with triflic anhydride in the presence of the hindered base 2,6-di-tert-butyl-4-methylpyridine. This reaction also produced the by-product 3,5-diene (3) in 10% yield. The 3-pyridyl group was then introduced into the 17-position by reacting (2) with diethyl(3-pyridyl)borane in THF, using bis(triphenylphosphine) palladium(II) chloride as a catalyst (0.01 equiv) and aqueous Na2CO3 as a nucleophilic activator to give the acetate (1) in 84% isolated yield. If (3) was not removed from the reaction mixture, the 3-pyridyl derivative (4) was similarly obtained. The acetyl group of (2) was reportedly stable to the mildly basic conditions of the coupling reaction (U.S. Pat. No. 5,604,213; Potter G A et al., J. Med. Chem. (1995), 38, 2463-2471).
Potter et al. (1995) found that the catalyst Pd(PPh3)2Cl2 was superior to Pd(PPh3)4 and consistently gave better yields of the coupled product. The catalyst could also be used at much lower levels, and reportedly even at 0.001 equiv, good yields were obtained with prolonged reaction times. Of importance was that this reaction did not require anhydrous conditions, and indeed an aqueous THF solvent system was employed.
Nevertheless, this procedure has several potential drawbacks as a method for large-scale synthesis. Aside from the use of the expensive and noxious triflic anhydride, the formation of the enol triflate requires use of the costly hindered base 2,6-di-tert-butyl-4-methylpyridine. Furthermore, the reaction was accompanied by some elimination of acetic acid to give androsta-3,5,16-trien-17-yl triflate which required chromatographic separation from the desired product, and contributed to reducing the isolated yield of the 3-acetate of dehydroepiandrosterone to a moderate 58%. These problems prompted consideration of an alternative steroidal precursor suitable for the cross-coupling reaction.
U.S. Pat. No. 5,604,213 and Potter, G A et al. Organic Preparations and Procedures International: The New Journal for Organic Synthesis (1997), 29:1, 123-128, disclose another method for Abiraterone acetate synthesis based on steroidal vinyl halides such as iodide (6) (Scheme 2):

Such steroidal vinyl iodides (6) are easily obtained from the corresponding 17-hydrazones (D. H. R. Barton, et al. J. Chem. Soc., (1962), 470; D. H. R. Barton, et al. Tetrahedron Lett. (1983), 24, 1605; Derek H. R. Barton, et al. Tetrahedron (1988), 44, 147).
The palladium catalyzed cross-coupling reaction of (6) with diethyl(3-pyridyl) borane conveniently proceeded without the need to protect the 3-hydroxyl function to give (7), whereas the use of an enol triflate in the coupling reaction does not allow this option. However, coupling with the iodide was much slower, requiring 4 days at 80° as compared with the 1 hr required when an enol triflate precursor was used. Moreover, the prolonged reaction time required for the cross-coupling reaction using the vinyl iodide (6) had enabled a Heck-type reaction to occur between the initial product (7) and the bis(triphenylphosphine)-palladium derivative of (6) to form by-product (8) and its acetylated form (9), which can be separated from Abiraterone only by reverse phase chromatography (Potter et al. 1997) (Scheme 3).

Both methods described above for Abiraterone preparation are accompanied by the formation of side products, which are very difficult to remove without tedious chromatographic purification.
WO 2006/021777 describes an improved route of Abiraterone acetate preparation in which the production of the undesirable by-product is reportedly kept down to acceptable levels (Scheme 4).

The formation of the triflate yielded the crude product in 80% yield with a product to starting material ratio of 3:1. The Suzuki reaction was performed on the crude product using a catalyst loading of 0.5 mol %. The product of the Suzuki reaction was isolated in a quantitative crude yield. Abiraterone acetate was purified by formation and crystallization of its methanesulfonate salt from EtOAc/MTBE. The salt was isolated in a 64% yield (7.65 g) and at 87.7% purity. This was subsequently recrystallized from a minimum volume of boiling isopropyl alcohol to yield the salt in 63% recovery and at 96.4% purity.
The method described in WO 2006/021777 uses expensive reagents (palladium based catalyst and diethyl-(3-pyridyl)borane). Palladium catalyst is used in homogeneous catalysis, which requires a stage of palladium capture by post-treatment of drug intermediate with modified silica. In addition, recovery of Abiraterone acetate base from the corresponding methanesulfonate salt can be accompanied by partial hydrolysis of the acetyl group, which results in yield reduction and requires subsequent acetylation of 3β-OH of the byproduct formed.
Therefore, there continues to be a need in the art for a practical method for making Abiraterone acetate, which not only avoids the problems of the existing art, but is also safe, cost effective, and industrially feasible.